Plasma proteomics reveals markers of metabolic stress in HIV infected children with severe acute malnutrition

Gerard Bryan Gonzales,Wieger Voskuijl,Bonface M. Gichuki,James A. Berkley,Isabel Potani,Robert H. J. Bandsma,Bijun Wen,James M. Njunge

doi:10.1038/s41598-020-68143-7

Abstract

HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.

Highlights

Malnutrition, undernutrition in all its forms, remains a global public health burden that accounts for 45% of all death among children under 5 years o ld[1]
Our results show that pathways involved in inflammatory response, complement cascade activation and lipid metabolism dysregulation are associated with human immunodeficiency virus (HIV) status
Our current study concurs with this finding, as we found reduced plasma levels of adiponectin in HIV(+) severe acute malnutrition (SAM) children compared to HIV(−) SAM children, along with upregulation of pathways involved in lipid transport and metabolism, very low-density lipoprotein assembly

Summary

Introduction

Malnutrition, undernutrition in all its forms, remains a global public health burden that accounts for 45% of all death among children under 5 years o ld[1]. HIV-infected or exposed children are significantly more likely to be stunted, wasted, and underweight[10]. They more often present with other clinical complications and greater susceptibility to infections, further complicating their clinical management, which may include providing more aggressive antimicrobial therapy and higher caloric nutritional intervention[11]. Mechanisms driving poor nutritional recovery of children with HIV even when detected co-morbidities are treated remain poorly understood[12]. Metabolic and other pathways which are likely to be involved in the response to infection, survival and nutritional recovery differ between children with SAM with and without HIV. We conducted a secondary analysis of clinical data and biological samples from a randomised clinical trial in Kenya and M alawi[13]

Methods

Results

Discussion

Conclusion